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Actualización en sedación octubre 2014, WHAT´S NEW ON SEDATION IN ICU
1. CICLO DE FORMACIÓN CONTINUA
UNIDAD DE CUIDADOS INTENSIVOS
ACTUALIZACIÓN EN SEDACIÓN
Juan Pablo González V.
Medicina de Urgencias
USACH-HRR
Tutor: Dra. Daniela Soto
Medicina Interna
UCI HRR
5. DELIRIUM
CONCEPTOS
• EL DELIRIUM MATA (A)
• EL DELIRIUM AUMENTA EL DETERIORO COGNITIVO (B)
• EL DELIRIUM AUMENTA LOS DÍAS DE HOSPITALIZACIÓN (A)
• EL DELIRIUM AUMENTA LOS COSTOS
Barr J, Fraser G. Clinical practice guidelines for the management of pain,
agitation, and delirium in adult patients in the intensive care unit.
Crit Care Med. 2013 Jan;41(1):263-306.
6. CONCEPTOS
INTERRUPCIÓN DIARIA DE SEDACIÓN
Y PROTOCOLOS
MENOS DÍAS ESTADÍA
MENOS DÍAS VM
Kress JP et al. Daily interruption of sedative infusions in critically ill patients undergoing
mechanical ventilation. N Engl J Med 2000, 342:1471-1477.
Brook AD et al. Effect of a nursing implemented sedation protocol on the duration of
mechanical ventilation. Crit Care Med 1999, 27:2609-2615
7. CONCEPTOS
SOBRESEDACIÓN MAYOR MORTALIDAD
Girard TD et al. Efficacy and safety of a paired sedation and ventilator weaning protocol
for mechanically ventilated patients in intensive care (Awakening and Breathing
Controlled trial: a randomised controlled trial. Lancet 2008;371:126–134.
Shehabi Y, Bellomo R et al. Sedation Practice in Intensive Care Evaluation (SPICE) Study
Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long
term mortality in ventilated critically ill patients. Am J Respir Crit Care Med
2012;186:724–731
Shehabi Y, Chan L et al. Sedation Practice in Intensive Care Evaluation (SPICE) Study
Group investigators. Sedation depth and long-term mortality in mechanically ventilated
critically ill adults: a prospective longitudinal multicentre cohort study. Intensive Care
Med 2013;39:910–918
8. MIDAZOLAM
DROGAS
• SINDROME DE DESCONTINUACIÓN
• RECUPERACIÓN RETARDADA POR
ACUMULACIÓN (FALLA RENAL)
Hughes MA et al. Context-sensitive half-time in multicompartment
pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology
1992;76:334–341
9. LORAZEPAM – MIDAZOLAM
DROGAS
Factores de riesgo independientes para
DELIRIUM
Pandharipande PP, Pun BT, et al. Effect of sedation with dexmedetomidine vs lorazepam
on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized
controlled trial. JAMA 2007;298:2644–2653.
Pisani MA, Murphy TE, et al. Benzodiazepine and opioid use and the duration of
intensive care unit delirium in an older population. Crit Care Med 2009;37:177–183
Pandharipande P et al. Lorazepam is an independent risk factor for transitioning to
delirium in intensive care unit patients. Anesthesiology 2006;104:21–26.
10. BENZODIACEPINAS
DROGAS
PEORES RESULTADOS :
SOBRESEDACIÓN, DELIRIUM, RETRASO DE EXTUBACIÓN,
ESTADÍAS EN UCI PROLONGADAS Y COSTOSAS
Breen D, Karabinis A. Decreased duration of mechanical ventilation when comparing analgesia-based
sedation using remifentanil with standard hypnotic-based sedation for up to 10 days in
intensive care unit patients: a randomised trial. Crit Care 2005.
Pandharipande, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain
dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA
2007;298:2644–2653.
Carson SS, et al. A randomized trial of intermittent lorazepam versus propofol with daily
interruption in mechanically ventilated patients. Crit Care Med 2006; 34:1326–1332.
11. PROPOFOL
DROGAS
• EFECTOS DOSIS DEPENDIENTES
• RECUPERACIÓN MÁS RAPIDA, SIN ACUMULACIÓN
• HIPERTRIGLICERIDEMIA
• DEPRESIÓN CARDIOVASCULAR
• SD DE INFUSIÓN DE PROPOFOL
• MAYOR COSTO
12. MODELO PK
MULTICOMPARTAMENTAL
DROGAS
Hughes MA et al. Context-sensitive half-time in multicompartment
pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology
1992;76:334–341
13. DROGAS
Sanders RD et al. Benzodiazepine augmented g-amino-butyric acid signaling
increases mortality from pneumonia in mice. Crit Care Med 2013;41:1627–1636.
14. DROGAS
BENZODIACEPINAS
EFECTOS INMUNOMODULADORES
ESTIMULACIÓN rGABA
Producción citokinas
Fagocitosis bacteriana
Obiora E, Sanders RD et al. The impact of benzodiazepines on occurrence of pneumonia
and mortality from pneumonia: a nested case-control and survival analysis in a population
based cohort. Thorax 2013;68:163–170.
Sanders RD et al. Benzodiazepine augmented g-amino-butyric acid signaling
increases mortality from pneumonia in mice. Crit Care Med 2013;41:1627–1636.
15. Dexmedetomedina DROGAS
• α2-AGONISTA
• MECANISMO DE ACCIÓN UNICO
• SEDANTE – ANALGESICO – SIMPATICOLÍTICO
• HIPOTENSIÓN
• BRADICARDIA
Myatra et al. Dexmedetomidine: Toward a paradigm shift in ICU sedation.
Indian J Crit Care Med. May 2014; 18(5): 271–272.
16. PUNTOS CLAVE
• EXISTE UNA ACTIVA DISCUSIÓN SOBRE LA
SEDACIÓN EN UCI – TEMA NO ACABADO
• EL DELIRIUM DAÑA A LOS PACIENTES
• HAY EVIDENCIA DE QUE LAS
BENZODIACEPINAS POR DIVERSOS
MECANISMOS PODRÍAN SER DELETÉREAS
18. EVIDENCIA
EVIDENCIA
“SE SUGIERE PREFERIR NO
BENZODIAZEPINICOS PARA SEDACIÓN PARA
MEJORAR RESULTADOS EN PACIENTES ADULTOS
EN VENTILACIÓN MECANICA” (2B)
20. EVIDENCIA
EVIDENCIA
Lonardo NW et al. Propofol is associated with favorable outcomes compared to
benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care
Med 2014;189: 1383–1394.
21. EVIDENCIA
• BASE DE DATOS IMPACT
• RETROSPECTIVO, COHORTE
• PAREAMIENTO POR PROPENSIÓN
Lonardo NW et al. Propofol is associated with favorable outcomes compared to
benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care Med
2014;189: 1383–1394.
22. EVIDENCIA
• VENTILACIÓN MECANICA
• Analisis pareado 1:1
Infusión contínua sedante único
PROPOFOL VS MIDAZOLAM (2250 c/u)
PROPOFOL VS LORAZEPAM (1054 c/u)
Lonardo NW et al. Propofol is associated with favorable outcomes compared to
benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care Med
2014;189: 1383–1394.
23. MORTALIDAD
EVIDENCIA
MIDAZOLAM VS PROPOFOL
Lonardo NW et al. Propofol is associated with favorable outcomes compared to
benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care
Med 2014;189: 1383–1394.
24. MORTALIDAD – TRAQUEOSTOMÍA
NEUMONIA
EVIDENCIA
LORAZEPAM VS PROPOFOL
Lonardo NW et al. Propofol is associated with favorable outcomes compared to
benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care
Med 2014;189: 1383–1394.
27. DEPENDENCIA DE
VENTILACIÓN
PROPOFOL MDZ P
EVIDENCIA
WEANING (+)
(DIA 28) 84,4% 75.1% < 0,001
PROPOFOL LRZ P
WEANING (+)
(DIA 28) 84,3% 78,8% < 0,001
Lonardo NW et al. Propofol is associated with favorable outcomes compared to
benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care
Med 2014;189: 1383–1394.
28. EVIDENCIA ESTADÍA ICU
PROPOFOL MDZ P
ALTA DE UCI
(DIA 28) 78,9% 69,5% < 0,001
PROPOFOL MDZ P
ALTA DE UCI
(DIA 28) 78,9% 69,5% < 0,001
Lonardo NW et al. Propofol is associated with favorable outcomes compared to
benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care
Med 2014;189: 1383–1394.
29. NEUMONIA
PROPOFOL LRZP P
EVIDENCIA
NEUMONIA 7,9% 12,7% < 0,001
ASOCIADA VM
Lonardo NW et al. Propofol is associated with favorable outcomes compared to
benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care
Med 2014;189: 1383–1394.
30. PUNTOS CLAVE DEL ESTUDIO
EVIDENCIA
• EL USO DE BENZODIAZEPINAS PARA SEDACIÓN EN
UCI PODRÍA GENERAR PEORES RESULTADOS
COMPARADO CON PROPOFOL
• EN MORTALIDAD, TIEMPO DE VM, TIEMPO DE
ESTADÍA, NECESIDAD DE TRAUEOSTOMÍA Y
NEUMONIA AVM
Lonardo NW et al. Propofol is associated with favorable outcomes compared to
benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care
Med 2014;189: 1383–1394.
32. EVIDENCIA
• UN CENTRO, RANDOMIZADO, ABIERTO
West China Hospital of Sichuan University
Zhou et al. Midazolam and propofol used alone or sequentially for long-term sedation
in critically ill, mechanically ventilated patients: a prospective, randomized study.
Critical Care 2014, 18:R122
33. TRES GRUPOS
FENTANILO Bolo 1 to 2 μg/kg
BIC 1 to 2 μg/kg/hr
INTERRUPCIONES DIARIAS
TODOS
+
MIDAZOLAM (M)
PROPOFOL (P)
MIDAZOLAM-PROPOFOL
(M-P)
EVIDENCIA
34. EVIDENCIA
1. GRUPO MIDAZOLAM
Bolo 0.03 - 0.30 mg/kg
BIC 0.04 - 0.20 mg/kg/hr
2. GRUPO PROPOFOL
Bolo 0.50 - 3mg/kg
BIC 0.50 - 3 mg/kg/hr
Zhou et al. Midazolam and propofol used alone or sequentially for long-term sedation
in critically ill, mechanically ventilated patients: a prospective, randomized study.
Critical Care 2014, 18:R122
35. EVIDENCIA
EVIDENCIA
GRUPO MIDAZOLAM - PROPOFOL
PRIMERO Midazolam LUEGO: Propofol
CRITERIOS DE CAMBIO:
Pa O2 > 60 mmHg
FiO2 < 50%
PEEP < 10
ESTABILIDAD HEMODINAMICA: NO ISQUEMIA MIOCARDICA NI
HIPOTENSIÓN
Dobuta < 5 μg/kg/min
Norepinefrina ≤2 μg/min
Zhou et al. Midazolam and propofol used alone or sequentially for long-term sedation
in critically ill, mechanically ventilated patients: a prospective, randomized study.
Critical Care 2014, 18:R122
36. EVIDENCIA EVIDENCIA
RESULTADOS
Zhou et al. Midazolam and propofol used alone or sequentially for long-term sedation
in critically ill, mechanically ventilated patients: a prospective, randomized study.
Critical Care 2014, 18:R122
37. EVIDENCIA EVIDENCIA
COSTOS
Zhou et al. Midazolam and propofol used alone or sequentially for long-term sedation
in critically ill, mechanically ventilated patients: a prospective, randomized study.
Critical Care 2014, 18:R122
38. RECUERDOS
EEVVIDIEDNECNIACIA
Zhou et al. Midazolam and propofol used alone or sequentially for long-term sedation
in critically ill, mechanically ventilated patients: a prospective, randomized study.
Critical Care 2014, 18:R122
39. PUNTOS CLAVE DEL ESTUDIO
EVIDENCIA
• UN PROTOCOLO COMBINADO DE SEDACIÓN CON
MIDAZOLAM – PROPOFOL PODRÍA TENER MEJORES
RESULTADOS EN UCI
• EN TIEMPO DE ESTADÍA, TIEMPO DE VENTILACIÓN
MECÁNICA, COSTOS Y CANTIDAD DE RECUERDOS
TRAUMÁTICOS
Zhou et al. Midazolam and propofol used alone or sequentially for long-term sedation
in critically ill, mechanically ventilated patients: a prospective, randomized study.
Critical Care 2014, 18:R122
41. NUESTRO PROTOCOLO
• Escasa adherencia
ENCUESTA ¿Por qué no usa el protocolo de sedación?
Los residentes no lo indican
Se inicia y después es cambiado por el residente
No se indica por escalón de sedación
Porque no sirve – dosis muy bajas – respuesta inadecuada
Nunca se a discutido ni actualizado
Dosis se calculan por pero estimado y no real
42. CONCLUSIONES
• LA MEJOR ESTRATEGIA DE SEDACIÓN EN UCI ES UN TEMA EN
DISCUSIÓN
• EXISTE EXTENSA EVIDENCIA EL USO DE BENZODIAZEPINAS
PODRÍA SER DELETÉREO, INCLUSO CON EFECTO EN
MORTALIDAD
• PROPOFOL PARECE SER UNA BUENA ALTERNATIVA
43. CONCLUSIONES
• EL USO DE UN PROTOCOLO COMBINADO PODRÍA
MINIMIZAR EL RIESGO DE LAS BZD Y GENERAR MEJORES
RESUTADOS CLÍNICOS Y ECONÓMICOS
• HAY POCA ADHERENCIA A NUESTRO PROTOCOLO. ¿SERÁ
MOMENTO DE ANALIZAR EL TEMA?
Kress JP, Pohlman AS, O’Connor MF, Hall JB: Daily interruption of sedative
infusions in critically ill patients undergoing mechanical ventilation. N Engl
J Med 2000, 342:1471-1477.
5. Brook AD, Ahrens TS, Schaiff R, Prentice D, Sherman G, Shannon W, Kollef MH:
Eff ect of a nursing implemented sedation protocol on the duration of
mechanical ventilation. Crit Care Med 1999, 27:2609-2615
10. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun
BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, et al. Efficacy
and safety of a paired sedation and ventilator weaning protocol
for mechanically ventilated patients in intensive care (Awakening
and Breathing Controlled trial): a randomised controlled trial.
Lancet 2008;371:126–134.
11. Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C,
Seppelt IM, Webb S, Weisbrodt L; Sedation Practice in Intensive Care
Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group.
Early intensive care sedation predicts long-term mortality in ventilated
critically ill patients. Am J Respir Crit Care Med 2012;186:724–731.
12. Shehabi Y, Chan L, Kadiman S, Alias A, Ismail WN, Tan MA, Khoo TM,
Ali SB, Saman MA, Shaltut A, et al.; Sedation Practice in Intensive
Care Evaluation (SPICE) Study Group investigators. Sedation
depth and long-term mortality in mechanically ventilated critically ill
adults: a prospective longitudinal multicentre cohort study. Intensive
Care Med 2013;39:910–918.
Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, Shintani AK, Thompson JL, Jackson JC, Deppen SA, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007;298:2644–2653.
Pisani MA, Murphy TE, Araujo KL, Slattum P, Van Ness PH, Inouye SK. Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population. Crit Care Med 2009;37:177–183.
14. Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW. Lorazepam is an independent risk factor
for transitioning to delirium in intensive care unit patients.
Anesthesiology 2006;104:21–26.
15. Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr,
Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of
mortality in mechanically ventilated patients in the intensive care unit.
JAMA 2004;291:1753–1762.
16. Shehabi Y, Riker RR, Bokesch PM, Wisemandle W, Shintani A, Ely EW; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients. Crit Care Med 2010;38:2311–2318.
17. Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med 2009;180:1092–1097
Carson SS, Kress JP, Rodgers JE, Vinayak A, Campbell-Bright S,
Levitt J, Bourdet S, Ivanova A, Henderson AG, Pohlman A, et al. A
randomized trial of intermittent lorazepam versus propofol with daily
interruption in mechanically ventilated patients. Crit Care Med 2006;
34:1326–1332.
3. Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR,
Shintani AK, Thompson JL, Jackson JC, Deppen SA, et al. Effect of
sedation with dexmedetomidine vs lorazepam on acute brain
dysfunction in mechanically ventilated patients: the MENDS
randomized controlled trial. JAMA 2007;298:2644–2653.
4. Breen D, Karabinis A, Malbrain M, Morais R, Albrecht S, Jarnvig IL,
Parkinson P, Kirkham AJ. Decreased duration of mechanical
ventilation when comparing analgesia-based sedation using
remifentanil with standard hypnotic-based sedation for up to 10 days
in intensive care unit patients: a randomised trial [ISRCTN47583497].
Crit Care 2005;9:R200–R210. (ISRCTN47583497).
Hughes MA, Glass PS, Jacobs JR. Context-sensitive half-time in
multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology 1992;76:334–341. Midazolam, for example, has a significantly longer context-sensitive half-time than propofol (9).
recent studies suggest that benzodiazepines have immunomodulatory effects that may be deleterious to patients with life-threatening infections. Animal research, for example, revealed critical impairments in immune function, including cytokine production and bacterial phagocytosis and killing, in mice treated with a benzodiazepine (19). These changes resulted from benzodiazepine stimulation of GABAA receptors expressed on immune cells and led to increased mortality and bacterial load from pneumococcal pneumonia. Additionally, observational and randomized studies of humans have noted worse infection-related outcomes in patients who received benzodiazepines
3. Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, Shintani AK, Thompson JL, Jackson JC, Deppen SA, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007;298:2644–2653.
19. Sanders RD, Godlee A, Fujimori T, Goulding J, Xin G, Salek-Ardakani S, Snelgrove RJ, Ma D, Maze M, Hussell T. Benzodiazepine augmented g-amino-butyric acid signaling increases mortality from pneumonia in mice. Crit Care Med 2013;41:1627–1636.
20. Obiora E, Hubbard R, Sanders RD, Myles PR. The impact of benzodiazepines on occurrence of pneumonia and mortality from pneumonia: a nested case-control and survival analysis in a population-based cohort. Thorax 2013;68:163–170.
21. Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, Herr DL, Maze M, Ely EW; MENDS investigators. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care 2010;14:R38.
recent studies suggest that benzodiazepines have
immunomodulatory effects that may be deleterious to patients with
life-threatening infections. Animal research, for example, revealed
critical impairments in immune function, including cytokine
production and bacterial phagocytosis and killing, in mice treated
with a benzodiazepine (19). These changes resulted from
benzodiazepine stimulation of GABAA receptors expressed on
immune cells and led to increased mortality and bacterial load
from pneumococcal pneumonia. Additionally, observational and
randomized studies of humans have noted worse infection-related
outcomes in patients who received benzodiazepines
3. Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR,
Shintani AK, Thompson JL, Jackson JC, Deppen SA, et al. Effect of
sedation with dexmedetomidine vs lorazepam on acute brain
dysfunction in mechanically ventilated patients: the MENDS
randomized controlled trial. JAMA 2007;298:2644–2653.
19. Sanders RD, Godlee A, Fujimori T, Goulding J, Xin G, Salek-Ardakani S,
Snelgrove RJ, Ma D, Maze M, Hussell T. Benzodiazepine augmented
g-amino-butyric acid signaling increases mortality from pneumonia
in mice. Crit Care Med 2013;41:1627–1636.
20. Obiora E, Hubbard R, Sanders RD, Myles PR. The impact of
benzodiazepines on occurrence of pneumonia and mortality from
pneumonia: a nested case-control and survival analysis in
a population-based cohort. Thorax 2013;68:163–170.
21. Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL,
Shintani AK, Herr DL, Maze M, Ely EW; MENDS investigators. Effect
of dexmedetomidine versus lorazepam on outcome in patients with
sepsis: an a priori-designed analysis of the MENDS randomized
controlled trial. Crit Care 2010;14:R38.
recent clinical practice guidelines (5) to recommend
“nonbenzodiazepine sedatives (either propofol or dexmedetomidine)”
for sedation in the ICU instead of benzodiazepines—
Lonardo, Mone, Nirula, et al.: Propofol vs. Benzodiazepines in Ventilated ICU Patients 1383
Lonardo NW, Mone MC, Nirula R, Kimball EJ, Ludwig K, Zhou X, Sauer BC, Nechodom K, Teng C, Barton RG. Propofol is associated with favorable outcomes compared to benzodiazepines in ventilated intensive care unit patients. Am J Respir Crit Care Med 2014;189: 1383–1394.
This type of study model is especially well suited to examine the outcomes of sedatives used in the ICU because of the well-known
variability of their use (29–31) that may not be apparent in a controlled study environment. A limitation of randomized, controlled sedation studies is that they often exclude patients, such as those with renal and/or liver dysfunction and hemodynamic instability. These critically ill patients are especially vulnerable to the adverse effects of continuous-infusion benzodiazepines because of potentially reduced hepatic clearance, renal insufficiency, and accumulation of active metabolites (24). In a natural ICU practice setting, continuous-infusion sedatives are commonly used in patients with organ dysfunction. By comparison, in the metaanalysis by Ho and Ng (25), patients with renal or liver dysfunction were excluded in half of the randomized trials
Figure 4. Cumulative incidence of intensive care unit (ICU) discharge over 28 days in the presence of competing risk event (mortality) for matched midazolam- and lorazepam-treated patients compared with propofol-treated patients.
Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008; 371: 126-134
Data are expressed as median (interquartile range) for non-normally distributed data or number (%) for nominal data. Kruskal–Wallis analysis of variance was used for non-normally distributed data comparisons, and the nominal data comparisons were based on either the chi-squared test or Fisher's exact test. In the presence of a significant difference in the three groups (P < 0.05), the parameters between any two groups were further compared with the value of α adjusted to 0.017. AKI, acute kidney injury; CRRT, continuous renal replacement therapy. aMedazolam sedation times of group M and group M-P were analyzed byindependent two-sample t test. bTime from the stopping of sedation until awake: missing assessments for the patients withdrawing from treatment or suffering from therapeutic failure (four patients in group M, six patients in group P, and three patients in group M-P). cTime from the stopping of sedation until extubation: exposure calculation was based on patients completing treatment (including 37 patients in group M, 35 patients in group P, and 32 patients in group M-P), patients withdrawing treatment and suffering therapeutic failure, and those who underwent tracheostomy without determining the extubation.
Data expressed as median (interquartile range). Kruskal–Wallis analysis of variance was used for data comparison. In the presence of significant difference in the
three groups (P < 0.05), the parameters between any two groups were further compared with the value of α adjusted to 0.017.
Data expressed as number (percentage). Data comparisons were based on the chi-squared test. In the presence of significant difference in the three groups
(P < 0.05), the parameters between any two groups were further compared with the value of α adjusted to 0.017.
Their analysis of a large, heterogeneous population not only improved statistical power but also enhances the generalizability of their findings.
Just as important, by using 1:1 propensity matching based on 15 Pretreatment covariates that were considered predictive of propofol use, the authors attempted to account for potential selection bias by creating comparator groups that were similar with regard to these measured covariates. Propensity score matching is a powerful technique used to reduce bias in observational studies in critical care and many other areas of research
25. Ho KM, Ng JY. The use of propofol for medium and long-term
sedation in critically ill adult patients: a meta-analysis. Intensive Care
Med 2008;34:1969–1979.